8qn7

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Amyloid-beta 40 doublet filament from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathyAmyloid-beta 40 doublet filament from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy

Structural highlights

8qn7 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 2.7Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B4DM00_HUMAN Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.[RuleBase:RU367156]

Publication Abstract from PubMed

We used electron cryo-microscopy (cryo-EM) to determine the structures of Abeta40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. In agreement with previously reported structures, which were solved to a resolution of 4.4 A, we found three types of filaments. However, our new structures, solved to a resolution of 2.4 A, revealed differences in the sequence assignment that redefine the fold of Abeta40 peptides and their interactions. Filaments are made of pairs of protofilaments, the ordered core of which comprises D1-G38. The different filament types comprise one, two or three protofilament pairs. In each pair, residues H14-G37 of both protofilaments adopt an extended conformation and pack against each other in an anti-parallel fashion, held together by hydrophobic interactions and hydrogen bonds between main chains and side chains. Residues D1-H13 fold back on the adjacent parts of their own chains through both polar and non-polar interactions. There are also several additional densities of unknown identity. Sarkosyl extraction and aqueous extraction gave the same structures. By cryo-EM, parenchymal deposits of Abeta42 and blood vessel deposits of Abeta40 have distinct structures, supporting the view that Alzheimer's disease and cerebral amyloid angiopathy are different Abeta proteinopathies.

Cryo-EM structures of Abeta40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy.,Yang Y, Murzin AG, Peak-Chew S, Franco C, Garringer HJ, Newell KL, Ghetti B, Goedert M, Scheres SHW Acta Neuropathol Commun. 2023 Dec 4;11(1):191. doi: 10.1186/s40478-023-01694-8. PMID:38049918[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. Yang Y, Murzin AG, Peak-Chew S, Franco C, Garringer HJ, Newell KL, Ghetti B, Goedert M, Scheres SHW. Cryo-EM structures of Aβ40 filaments from the leptomeninges of individuals with Alzheimer's disease and cerebral amyloid angiopathy. Acta Neuropathol Commun. 2023 Dec 4;11(1):191. PMID:38049918 doi:10.1186/s40478-023-01694-8

8qn7, resolution 2.70Å

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OCA